Barry P. Rosen is currently Distinguished University Professor at the Herbert Wertheim College of Medicine, Florida International University in Miami, Florida since 2009. He was Associate Dean for Basic Research and Graduate Programs from 2009-2016. For 22 years he was Chair and Distinguished Professor of Biochemistry and Molecular Biology at Wayne State University School of Medicine in Detroit, Michigan. He received his B.S. from Trinity College, Hartford, Connecticut in 1965 and his M.S. (1968) and Ph.D. (1969) from the University of Connecticut and was an NIH postdoctoral fellow at Cornell University (1969-1971). He was on the faculty at the University of Maryland School of Medicine in Baltimore, Maryland for 15 years. For four decades his laboratory has investigated the mechanisms of transport and detoxification of transition metals, heavy metals and metalloids in bacteria, yeast, protozoans, mammals and plants. He identified the pathways of arsenic uptake, efflux, biotransformation and regulation in organisms from E. coli to humans. He identified most of the known arsenic detoxification genes and characterized their gene products at the biochemical and structural level. He solved the crystal structure of the ArsA As(III)-translocating ATPase, the ArsR repressor orthologue CadC, the ArsC and LmAcr2 arsenate reductases, the ArsH NADPH-FMN oxidoreductase, the ArsD As(III) metallochaperone, the ArsM As(III)-SAM methyltransferases from Cyanidioschyzon merolae and Chlamydomonas reinhardtii and most recently the ArsI C-As lyase. He identified and named the ArsR family of metalloregulatory proteins. He made the seminal discovery that aquaglyceroporin channels, from E. coli GlpF to human AQP9, are the transporters that nearly every cell uses to take up As(III). He is currently elucidating the enzymes and transporters of the arsenic biomethylation and organoarsenical redox cycles. He has published more than 325 papers, reviews and books. He is the recipient of numerous awards, including Basil O'Connor Award from the March of Dimes, Maryland Distinguished Young Scientist Award, Josiah Macy, Jr. Faculty Scholar Award, Gershenson Distinguished Faculty Fellow Award (WSU), Outstanding Graduate Mentor Award (WSU) and Lawrence Weiner Medical Alumni Award (WSU). He has been continuously funded by NIH and NSF since 1972 and was the holder of a prestigious MERIT Award from the National Institute of Health. He has been on many national and international panels at NIH, NSF, and American Heart Association, and on multiple editorial boards, and recently was a reviewer of the FDA policy on arsenic in rice. He was elected President of the Association of Medical and Graduate Departments of Biochemistry, the national organization of biochemistry departments, and is an elected fellow of both he American Society for Microbiology (ASM) and the American Association for the Advancement of Science (AAAS).
Current research projects
- NIH R01 GM55425-35, Mechanisms of arsenic biotransformations and transport, The overall goal of research in the this project is a detailed molecular analysis of the arsenic transporters and modifying enzymes, especially microbial pathways of arsenic biotranformations by methylation, demethylation, oxidation and reduction. Arsenic, a Group 1 human carcinogen, ranks first on the EPA's Superfund list. Arsenic enters the human body from both geological and anthropogenic sources. Because of the ubiquity of arsenic in the environment, every organism has developed transport systems for the efflux and detoxification of arsenic. Chronic exposure to arsenic has been linked to cardiovascular and peripheral vascular diseases, neurological disorders, diabetes and various cancers. Arsenic-containing drugs are used as chemotherapeutic agents for the treatment of leukemia and parasitic diseases. An understanding of both arsenic chemistry and the molecular details of arsenic transport systems is essential for alleviating the problems of arsenic toxicity, as well as for the rational design of drugs to treat drug-resistant microbes and cancer cells.
- NIH 1R01 ES023779-05, The human arsenic methylation pathway, The overall goal of this project is to elucidate the mechanisms and consequences of human methylation of arsenic. Arsenic is the most pervasive Group A human environmental carcinogen in nature. It is biomethylated by the liver enzyme As(III) S-adenosylmethionine (SAM) methyltransferase (AS3MT) (EC # 22.214.171.124) to mono- and dimethylated species. In humans arsenic methylation has been proposed to be a major contributor to arsenic carcinogenesis because the trivalent products methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)) are more carcinogenic than inorganic arsenite (As(III)). Individuals with AS3MT polymorphisms produce increased amounts of methylated species. It is not clear whether this increases the risk for arsenic-related diseases or, alternatively, lessen risk due to faster rates of clearance. How methylation contributes to carcinogenesis depends on the mechanism of the AS3MT enzyme and differences between wild type and polymorphic enzymes. The overall goal of this study is elucidation of the structure and function of human AS3MT and its polymorphic forms, with the following specific aims:
Recent publications (from more than 340 papers and reviews):
- Zhang, J., Xu, Y., Cao, T., Chen, J., Rosen, B.P. and Zhao, F.J. Arsenic methylation by a genetically engineered Rhizobium-legume symbiont. Plant Sci. 416, 259-269(2017). PMCID: PMC5889086
- Chen, J. and Rosen, B.P. Organoarsenical biotransformations by Shewanella putrefaciens. Environ Sci Technol. 50,7956-7963(2016). PCMID: PCM27366920
- Chen, J., Li, J., Jiang, X. and Rosen B.P. Conserved cysteine residues determine substrate specificity in a novel As(III) S-adenosylmethionine methyltransferase from Aspergillus fumigatus. Mol Microbiol. 104, 250-259 (2017). PCMID: PMC5380552
- Hao, X., Li, X., Pal, C., Hobman, J., Larsson, D.G., Saquib, Q., Alwathnani, H.A., Rosen, B.P., Zhu, Y.G., Rensing, C. Bacterial resistance to arsenic protects against protist killing. Biometals. 30,307-311 (2017). PMID: 28210928
- Chen, S.C., Sun, G.X., Rosen, B.P., Zhang, S.Y., Deng, Y., Zhu, B.K., Rensing C., Zhu, Y.G. Recurrent horizontal transfer of arsenite methyltransferase genes facilitated adaptation of life to arsenic. Sci Rep. 7, 7741 (2017).PMCID: PMC5552862
- Li, J., Packianathan, C., Rossman, T.G. and Rosen, B.P. Nonsynonymous polymorphisms in the human AS3MT arsenic methylation gene: implications for arsenic toxicity. Chem. Res. Toxicol. 30, 1481-1491 (2017) PMCID: Cover article.
- Pawitwar, S.S., Nadar, V.S., Kandegedara, A., Stemmler, T.L., Rosen, B.P. and Yoshinaga, M. Biochemical characterization of ArsI: a novel C-As lyase for degradation of environmental organoarsenicals. Environ. Sci. Technol. 51, 11115-11125 (2017). PMCID: PMC5870903
- Chen, J., Nadar, V.S. and Rosen, B.P. A novel MAs(III)-selective ArsR transcriptional repressor. Mol Microbiol. 106, 469-478 (2017). PMCID: PMC5653410. Cover article.
- Huang, K., Xu, Y., Packianathan, C., Gao, F., Chen, C., Zhang, J, Shen, Q., Rosen, B.P. and Zhao, F.J. Arsenic methylation by a novel ArsM As(III) S-adenosylmethionine methyltransferase that requires only two conserved cysteine residues.Mol Microbiol. 107, 265-276 (2018).PMCID: PMC5760297
- Packianathan, C., Li, J., Kandavelu, P., Sankaran, B. and Rosen, B.P. Reorientation of the methyl group in MAs(III) is the rate-limiting step in the ArsM As(III) S-adenosylmethionine methyltransferase reaction. ACS Omega. 3, 3104-3112 (2018). PMCID: PMC5870839
- Yoshinaga, M., How, S., Blanco, D, Murdoch, I.S., Grudny, M., Powers, S.L., Molina, N., Rosen, B.P., Welch, A.Z. Directed evolution of Saccharomyces cerevisiae for increased selenium accumulation. Microorganisms 6, E81 (2018). PMCID: PMC6165298.
- Packianathan, C., Kandavelu, P. and Rosen, B.P. The structure of an As(III) S-adenosylmethionine methyltransferase with 3-coordinately bound As(III) depicts the first step in catalysis. Biochemistry 57, 4083-4092 (2018). PMCID: PMC6172949
- Chen, J., Yoshinaga, M. and Rosen, B.P. The antibiotic action of methylarsenite is an emergent property of microbial communities. Molec. Microbiol. 11:487-494 (2019). PMCID: PMC6370046
- Xue, X.M., Ye, J., Raber, G., Rosen, B.P., Francesconi, K.A., Xiong, C., Zhu, Z., Rensing, C. and Zhu, Y.G. Identification of steps in the pathway of arsenosugar biosynthesis. Environ Sci Technol. 53,634–641. PMID: 30525501
- Nadar, V.S., Chen, J. Dheeman, D.S., Galvan, A.E., Yoshinaga-Sakurai, K. Kandavelu, P. Sankaran, B., Kuramata, M., Ishikawa, S., Rosen, B.P. and Yoshinaga, M. Arsinothricin, a novel arsenic-containing antibiotic. Nature Chem. Biol. In press 2019.